Enhancement of carboplatin toxicity by Pluronic block copolymers
Enhancement of carboplatin toxicity by Pluronic block copolymers
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DOI：
10.1016/j.jconrel.2005.04.015
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发表时间：
2005-08-18
影响因子：
10.8
通讯作者：
Teets, JM
中科院分区：
文献类型：
--
作者：
Exner, AA;Krupka, TM;Teets, JM
本研究的目的是研究三种Pluronic三嵌段共聚物（17127，P85或L61）对卡铂对DHB/K12/TRb大鼠结直肠癌细胞系的细胞毒性的影响。在聚合物浓度范围为0.0001-10% （w/w）的情况下，研究了增敏效应对Pluronic剂量的依赖性。为了确定Pluronic对卡铂的毒性及其潜在的增强作用，在恒定浓度Pluronic存在的情况下，以0-0.5% （w/w）的剂量将药物递送至细胞。这些治疗组与单独使用卡铂的对照组进行比较。用线粒体酶活性测定法（WST-1）测定处理后的细胞毒性，用May-Grunwald染色法和Giemsa染色法检测细胞形态。结果表明，P85对卡铂毒性的增强作用最大，抑制浓度（IC50）降低了50%（从单独卡铂的0.096 mg/mL降低到P85存在时的0.048 mg/mL）。L61对加药或不加药的细胞均有毒性（活性< 3.5%），而F127无致敏作用，在某些情况下比未加药的对照组细胞活性提高130%。处理后0和24 h的台盼蓝排斥细胞计数证实WST-1结果。数据最终证明Pluronic P85是增加卡铂细胞毒性的最佳药物，不仅可以作为药物传递方案，还可以作为未来癌症治疗的化学增敏剂。(c) 2005 Elsevier B.V.版权所有
The objective of this study was to examine the effects of three Pluronic triblock copolymers (17127, P85, or L61) on the cytotoxicity of carboplatin to the DHB/K12/TRb rat colorectal carcinoma cell line. Studies to determine the dependence of the sensitization effect on Pluronic dose were carried out for polymer concentrations ranging from 0.0001-10% (w/w). To establish the carboplatin toxicity and its potential enhancement by Pluronic, the drug was delivered to cells in doses ranging from 0-0.5% (w/w) in the presence of Pluronic at a constant concentration. These treatment groups were compared to control groups receiving carboplatin alone. Cell cytotoxicity resulting from the treatments was determined with a mitochondrial enzyme activity assay (WST-1), while cell morphology was examined with May-Grunwald and Giemsa staining. Results indicate that the greatest enhancement of carboplatin toxicity was induced by P85, where the inhibitory concentration (IC50) was reduced by 50% (from 0.096 mg/mL for carboplatin alone to 0.048 mg/mL in presence of P85). L61 was toxic to the cells with or without drug (viability < 3.5%), while F127 exhibited no sensitizing effect and in some cases increased the cell viability to 130% over the untreated control. The WST-1 results were confirmed by trypan blue exclusion cell counts at 0 and 24 h post treatment. Data conclusively demonstrate that Pluronic P85 is the optimal agent for increased cytotoxicity of carboplatin in this cell line and can potentially be used not only as a drug delivery scheme but also as a chemosensitizing agent in future cancer therapy. (c) 2005 Elsevier B.V. All rights reserved.